Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

Trial Profile

A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 18 Aug 2020

At a glance

  • Drugs Mavrilimumab (Primary)
  • Indications COVID 2019 infections; Inflammation; Pneumonia; Respiratory insufficiency
  • Focus Registrational; Therapeutic Use
  • Sponsors Kiniksa Pharmaceuticals
  • Most Recent Events

    • 19 Jul 2020 Planned initiation date changed from 1 Jun 2020 to 1 Jul 2020.
    • 19 Jul 2020 Status changed from not yet recruiting to recruiting.
    • 24 Jun 2020 Status changed from planning to not yet recruiting.

Trial Overview

Purpose

This Phase II/III trial will evaluate Mavrilimumab for the treatment of patients with COVID-19 pneumonia and hyperinflammation.

Kiniksa's Phase 2/3 clinical trial protocol is a global, randomized, double-blind, placebo-controlled study encompassing 2 phases of development (Phase 2 and Phase 3).

The Phase 2 portion of the trial is expected to enroll approximately 160 patients and is intended to evaluate the efficacy and safety of 2 dose levels of mavrilimumab relative to placebo in patients who have tested positive for COVID-19 and have x-ray/CT evidence of bilateral pneumonia, active or recent fever, and clinical laboratory results indicative of hyper inflammation.

The Phase 3 portion is expected to enroll approximately 420 patients and is intended to confirm Phase 2 efficacy and safety findings. In both Phase 2 and Phase 3, patients are expected to be enrolled into 2 cohorts: Cohort 1 will include non-intubated, hospitalized patients who require supplemental oxygen to maintain SpO2 = 92%, (i.e., non-mechanically ventilated patients); and Cohort 2 will include hospitalized patients for whom mechanical ventilation was recently initiated within 48 hours prior to randomization (i.e., ventilated patients).

Following screening, enrolled patients in each cohort will be randomized 1:1:1 to receive a single IV infusion of mavrilimumab 6mg/kg or 10 mg/kg or placebo (Day 1). The primary efficacy endpoint for the Phase 2 portion of the trial for Cohort 1 is the proportion of patients alive and without respiratory failure (defined as the need for high flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation) at Day 15 and for Cohort 2 is the mortality rate by Day 15.

There will be a seamless transition in enrollment of patients in both cohorts between the Phase 2 and Phase 3 portions of the trial. For each cohort, once the last patient in Phase 2 is enrolled, all subsequent patients will be considered Phase 3 patients. Once the last patient in Phase 2 completes Day 15, primary efficacy and safety analyses of the Phase 2 data will be conducted. Following demonstration of efficacy and safety in Phase 2, the Phase 3 portion of the trial will be continued/completed

Primary Endpoints

Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15

description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
time_frame: Day 15

Cohort 2: Mortality Rate at Day 15

description: Mortality rate is defined as the proportion of participants who die.
time_frame: Day 15

Other Endpoints

Cohort 1: Time to Return to Room Air by Day 15

description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 15

Cohort 1: Time to 2-point Clinical Improvement by Day 15

description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 15

Cohort 1: Mortality Rate at Day 29

description: Mortality rate is defined as the proportion of participants who die.
time_frame: Day 29

Cohort 1: Time to 1-Point Clinical Improvement by Day 15

description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 15

Cohort 2: Mortality Rate at Day 29

description: Mortality rate is defined as the proportion of participants who die.
time_frame: Day 29

Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15

description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
time_frame: Day 15

Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29

description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
time_frame: Day 29

Cohorts 1 and 2: Time to Return to Room Air by Day 29

description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 29

Cohort 2: Time to 2-point Clinical Improvement by Day 15

description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 15

Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29

description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 29

Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29

description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 29

Cohort 1: Respiratory Failure-Free Survival by Day 15

description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
time_frame: up to Day 15

Cohort 1: Respiratory Failure-Free Survival by Day 29

description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
time_frame: up to Day 29

Cohort 1: Proportion of Participants Who Return to Room Air by Day 15

description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 15

Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29

description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: up to Day 29

Cohort 1: Mortality Rate at Day 15

description: Mortality rate is defined as the proportion of participants who die.
time_frame: Day 15

Cohorts 1 and 2: Overall Survival by Day 29

description: Overall survival is defined as time from date of randomization to the date of death.
time_frame: up to Day 29

Cohorts 1 and 2: Clinical Status Over Time

description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: Days 4, 8, 15, 22, and 29

Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90

time_frame: through Day 90 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Inflammation treatment -
Pneumonia treatment severe
Respiratory insufficiency treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 580

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Key - Subject (or legally authorized representative) is able and willing to provide informed consent, which includes compliance with study requirements and restrictions listed in the consent form - Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization - Hospitalized for SARS-CoV-2 - Bilateral pneumonia on chest x-ray or computed tomography - Active fever or recently documented fever within 72 hours prior to randomization - Clinical laboratory results indicative of hyper-inflammation - Cohort 1: Receiving any form of oxygenation or NIV to maintain SpO2 ≥ 92% and not-intubated (examples include nasal cannula, face mask, venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation) - Cohort 2: Recently ventilated with mechanical ventilation prior to randomization Key

Patient Exclusion Criteria

- Onset of COVID-19 symptoms or positive COVID-19 test result > 14 days prior to randomization - Hospitalized > 7 days prior to randomization - Need for invasive mechanical ventilation (Only for Cohort 1) - Need for ECMO - Serious prior or concomitant illness that in the opinion of the Investigator precludes the subject from enrolling in the trial - Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12 months, cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil (MMF), COVID-19-immune plasma, or other immunosuppressant within 4 weeks prior to randomization - corrected QT interval Fridericia's formula (QTcF) on Screening electrocardiogram (ECG) ≥450 ms - Chronic or recent (within 7 days prior to randomization) corticosteroid use >10 mg/day

Trial Details

Identifiers

Identifier Owner
NCT04447469 ClinicalTrials.gov: US National Institutes of Health
KPL301C203 -

Organisations

  • Sponsors Kiniksa Pharmaceuticals
  • Affiliations Kiniksa Pharmaceuticals

Trial Dates

  • Initiation Dates

    Planned : 01 Jul 2020

    Actual : 27 Jul 2020

  • Primary Completion Dates

    Planned : 01 Feb 2021

  • End Dates

    Planned : 01 Apr 2021

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II/III
  • Location USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
MavrilimumabPrimary Drug Intravenous Infusion

10 mg/kg (Cohort 1)

Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

10 mg/kg (Cohort 2)

Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

6 mg/kg (Cohort 1)

Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

6 mg/kg (Cohort 2)

Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

Placebo (Cohort 1)

Non-mechanically ventilated participants administered placebo as a single IV infusion
Other: Placebo (matching placebo)

Placebo (Cohort 2)

Mechanically ventilated participants administered placebo as a single IV infusion
Other: Placebo (matching placebo)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Joshua Denson, MD Tulane Medical Center USA
Kiniksa Clinical Research Team
(781) 431-9100 clinicaltrials@kiniksa.com
show details
-
Madhu Pendurthi, MD Mercy Hospital USA
Mohammad Madjid, MD University of Texas Health Sciences USA
Tisha Wang, MD UCLA Medical Center USA

Centres

Centre Name Location Trial Centre Country
-
-
-
Kiniksa Pharmaceuticals, Ltd.
-
-
Mercy Hospital Springfield, Missouri USA
Tulane Medical Center New Orleans, Louisiana USA
UCLA Medical Center Los Angeles, California USA
University of Texas Health Sciences Houston, Texas USA

Trial History

Event Date Event Type Comment
18 Aug 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 18 Aug 2020
19 Jul 2020 Other trial event Planned initiation date changed from 1 Jun 2020 to 1 Jul 2020. Updated 22 Jul 2020
19 Jul 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 22 Jul 2020
29 Jun 2020 Other trial event New source identified and integrated ClinicalTrials.gov: (US National Institutes of Health: NCT04447469) Updated 22 Jul 2020
24 Jun 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 29 Jun 2020
08 Jun 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company announced an active investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) for this trial. Updated 10 Jun 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020
31 Mar 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company is engaging with the U.S. Food and Drug Administration (FDA) regarding the path forward for potential Phase 2/3 clinical development of mavrilimumab in COVID-19 pneumonia. Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Kiniksa Pharmaceuticals. Kiniksa Announces Early Evidence of Treatment Response with Mavrilimumab in 6 Patients with Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release
  3. Kiniksa Pharmaceuticals. Kiniksa Reports First Quarter 2020 Financial Results and Highlights Recent Corporate and Pipeline Activity. Media-Rel 2020;.

    Media Release
  4. Kiniksa Pharmaceuticals. Kiniksa Announces 28-Day Clinical Outcomes Data from Mavrilimumab Treatment Protocol in Severe COVID-19 Pneumonia and Active U.S. IND for Phase 2/3 Clinical Trial. Media-Rel 2020;.

    Media Release
Back to top